Despite the anatomical contiguity between the gastroesophageal and pharyngolaryngeal lumen, under normal condition the airway is protected from aspiration of gastric content. The mechanisms of this protection are not completely understood and as such the pathophysiologic mechanisms of related disorders remain uncertain because of either lack of proper techniques and instrumentations or suitable human and animal models for design of appropriate experiments. These shortcomings had now been remedied and our preliminary data suggests the feasibility and safety of these studies. We have identified a human model of defective airway protective reflexes and developed a feline model for studying interactions between esophagus and airway under physiologic and pathophysiologic conditions. We also have developed and successfully tested new recording devices and experimental techniques for use in both in human infants and adults as well as our feline model. Because the nature of these experiments requires expertise from multiple disciplines we have assembled a large multi-disciplinary research team comprised of experts from the Departments of Medicine, Neurology, Physiology, Radiology, Pediatric, and Otolaryngology to carry out the proposed studies in this project. This team has a long history of successful collaboration resulting in the discovery and characterization of several hitherto undescribed airway protective reflexes, development of newer methodology, and documentation of abnormalities of upper esophageal sphincter and glottal protective functions. The degree of interaction and collaboration among the members of this team pursuing their common goal is attested by their many joint publications of research outcomes over the past several years. The intense interest and the obvious need for better understanding of the mechanisms of upper gut and airway interaction coupled with the synergy and enthusiasm of our research team provided the basic impetus for the development of the current proposal. All of the projects in this program share the common theme of identifying, characterizing and quantitating the mechanisms that govern the physiologic and pathophysiologic interaction between the esophagus and the airway. The proposed program includes three subprojects and an administrative core. Project 1 is designed to investigate the relationship between the esophagus and tracheo-bronchial tree in a feline model. Project 2 studies the mechanism of prevention of aspiration in adult humans. Project 3 addresses the developmental physiology and pathophysiology of airway safety in infants.